West Nile virus (WNV) is an emerging mosquito-borne pathogen and is posing significant global health challenge through climate change. WNV, transmitted between birds and mosquitoes, has significantly expanded northward in recent years, leading to outbreaks across Europe and North America. This review explores the recent advancements and therapeutic strategies targeting WNV's structural and non-structural (NS) proteins, which play critical roles in viral replication and pathogenesis. Promising candidates include peptide-based inhibitors, monoclonal antibodies, and small molecules that disrupt protein-protein interactions. Most of current findings are derived from methods or assays, with limited validation through studies. Although no vaccines are currently available for humans, several have been approved for horses, and development efforts are ongoing. The growing threat of WNV underscores the urgent need for validated antiviral therapies and scalable vaccines, especially considering its increasing geographic range and public health impact.